维生素E和氨基胍在糖尿病肾病治疗中的协同作用

The Synergistic Effect of Vitamin E and Aminoguanidine on Diabetic Nephropathy

目的探讨维生素E和氨基胍在糖尿病肾病（DN）治疗中的协同作用。方法①以一次性腹腔注射链脲佐菌素（STZ，55mg／kg）诱导糖尿病大鼠模型，将大鼠分为正常对照组、糖尿病对照组、糖尿病加维生素E治疗组、糖尿病加氨基胍治疗组、糖尿病加维生素E加氨基胍治疗组；②观察1、2、4、8、12、16周时各组大鼠24h尿白蛋白排泄率（UAER），16周时各组大鼠尿素氮（BUN）、血肌酐（SCr）及肾组织病理改变情况；③观察各组大鼠16周时肾小球活性氧（ROS）聚集情况以及肾间质8-羟基脱氧鸟苷（8-OHDG）表达情况。结果与糖尿病组比较，维生素E治疗组在2周时UAER明显下降，但在4、8、12、16周时两组比较无统计学意义；氨基胍治疗组和两药合用组则在包括2周以后的各时间点UAER均较糖尿病组明显下降，且两药合用组UAER下降更明显。16周时各组间BUN、SCr差异无统计学意义。16周时糖尿病组大鼠肾小球系膜区增宽，系膜基质聚集；维生素E治疗组肾组织病理无改善，氨基胍治疗组略有改善，而两药合用组则有明显改善。16周时糖尿病组大鼠肾小球ROS聚集，肾间质8-OHDG表达增强，维生素E组肾组织ROS聚集和8-OHDG表达未减轻，氨基胍治疗有一定程度减轻，两药合用组肾组织ROS聚集和8-OHDG表达则明显减轻。结论维生素E和氨基胍在DN的治疗中具有协同作用，而这一协同作用可能通过协同抗氧化来实现。

Objective To investigate the synergistic effect of vitamin E and aminoguanidine on diabetic nephropathy. Method Wistar rats were divided into five groups ： normal rats, diabetic rats, diabetic rats treated with vitamin E, diabetic rats treated with aminoguanidine, diabetic rats treated both with vitamin E and aminoguanidine. Urinary albumin excretory rate （UAE） was measured on the 1, 2, 4, 8, 12 and 16th weeks of experiment. Blood urea nitrogen （BUN）, serum creatinine （Scr）, renal tissue pathology, glomerular reactive oxygen species （ROS） level and renal 8-OH-deoxyguanosine expression were detected on the 16th week of experiment. Results When comparing with diabetic rats, UAE was decreased in 2 weeks but was not different in 4, 8,12 and 16 weeks in vitamin E alone treatment group. Vitamin E alone also had no effect on renal tissue pathology, glomerular reactive oxygen species （ROS） level and renal 8-OH-deoxyguanosine expression. However, anminoguanidine alone or combined vitamin E and anminoguanidine therapy showed decreased UAE on second, 4^th, 8^th, 12^th and 16^th week, improved renal tissue pathology, ameliorated glomerular reactive oxygen species （ROS） level and renal 8-OH-deoxyguanosine expression were demonctraled after 16 weeks, but the effect of combined drugs therapy was more significant. Conclusions Vitamin E and aminoguanidine present syneigistic effect on diabetic nephropathy through synergistic prevention on oxidative stress in renal tissue.